Mesangial cell hyperplasia is a feature of several human glomerular diseases. The cause of this increased cell number is unknown. We assessed human mesangial cells in vitro and found that they possessed an insulin- like growth factor-I (IGF-I) receptor consisting of ` and a units (Mr 130k and 90k respectively). Fifty percent inhibition of IGF-I specific binding to the receptor required 1x10(-9)M IGF-I, 1x10(-6)M insulin, and 1x10(-)7M multiplication stimulating activity (MSA). Analysis of binding by the method of Scatchard revealed one type of IGF-I receptor with a kd=1.35x10(- 9)M, and a number per cell of 1.04x10(5). Binding studies on whole glomeruli was of similar specificity and there were 7.17x10(7) receptors per glomerulus (kd=1.12x10(-9)M). Examination of the effect of IGF-I on the cell cycle revealed that cells treated with platelet derived growth factor (PDGF) had a rapid (3)H-thymidine response which was abolished by anti-PDGF antibody. Finally, PDGF increased RNA and protein sysnthesis, which was not enhanced by IGF-I. In summary, human mesangial cells, and whole glomeruli, possess IGF-I specific receptors and IGF-I was found to act as a progression factor in the cell cycle.